PMID- 31063608
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20200526
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 106
IP  - 3
DP  - 2019 Sep
TI  - Macrophage priming is dispensable for NLRP3 inflammasome activation and 
      restriction of Leishmania amazonensis replication.
PG  - 631-640
LID - 10.1002/JLB.MA1118-471R [doi]
AB  - The NLRP3 inflammasome is activated in response to multiple stimuli and triggers 
      activation of caspase-1 (CASP1), IL-1beta production, and inflammation. NLRP3 
      activation requires two signals. The first leads to transcriptional regulation of 
      specific genes related to inflammation, and the second is triggered when 
      pathogens, toxins, or specific compounds damage cellular membranes and/or trigger 
      the production of reactive oxygen species (ROS). Here, we assess the requirement 
      of the first signal (priming) for the activation of the NLRP3 inflammasome in 
      bone marrow-derived macrophages (BMDMs) infected with Leishmania amazonensis. We 
      found that BMDMs express the inflammasome components NLRP3, ASC, and CASP1 at 
      sufficient levels to enable the assembly and activation of NLRP3 inflammasome in 
      response to infection. Therefore, priming was not required for the formation of 
      ASC specks, CASP1 activation (measured by fluorescent dye FAM-YVAD), and 
      restriction of L. amazonensis replication via the NLRP3 inflammasome. By 
      contrast, BMDM priming was required for CASP1 cleavage (p20) and IL-1beta secretion, 
      because priming triggers robust up-regulation of pro-IL-1beta and CASP11 that are 
      important for efficient processing of CASP1 and IL-1beta. Taken together, our data 
      shed light into the cellular and molecular processes involved in activation of 
      the NLRP3 in macrophages by Leishmania, a process that is important for the 
      outcome of Leishmaniasis.
CI  - (c)2019 Society for Leukocyte Biology.
FAU - de Carvalho, Renan V H
AU  - de Carvalho RVH
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
FAU - Silva, Alexandre L N
AU  - Silva ALN
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
FAU - Santos, Leonardo L
AU  - Santos LL
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
FAU - Andrade, Warrison A
AU  - Andrade WA
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
FAU - de Sa, Keyla S G
AU  - de Sa KSG
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
FAU - Zamboni, Dario S
AU  - Zamboni DS
AD  - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade 
      de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao 
      Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190507
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Pycard protein, mouse)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - CARD Signaling Adaptor Proteins/metabolism
MH  - Enzyme Activation
MH  - Inflammasomes/*metabolism
MH  - Interleukin-1alpha/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Leishmania mexicana/growth & development/*physiology
MH  - Leishmaniasis, Cutaneous/enzymology/immunology/parasitology
MH  - Ligands
MH  - Lipopolysaccharides
MH  - Macrophages/metabolism/*parasitology
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Parasites/growth & development
MH  - Receptors, Interleukin-1/metabolism
MH  - Toll-Like Receptors/agonists/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - Leishmaniasis
OT  - caspase-1
OT  - innate immunity
EDAT- 2019/05/08 06:00
MHDA- 2020/05/27 06:00
CRDT- 2019/05/08 06:00
PHST- 2019/01/07 00:00 [received]
PHST- 2019/04/10 00:00 [revised]
PHST- 2019/04/14 00:00 [accepted]
PHST- 2019/05/08 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/05/08 06:00 [entrez]
AID - 10.1002/JLB.MA1118-471R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2019 Sep;106(3):631-640. doi: 10.1002/JLB.MA1118-471R. Epub 2019 
      May 7.